In this report, we have discovered a novel signaling pathway within the tumor microenvironment (TME) downstream of the MCSF receptor, the extracellular matrix and the α4β1 integrin in which Rac2 is necessary and sufficient to control, in a macrophage autonomous manner, tumor progression including the processes of tumor growth, invasion, angiogenesis, metastasis and polarization of M2 macrophages. The gene discussed is RAC2; the disease is neoplasm.